A pharmaceutical composition for preventing and / or treating neuropathic pain or complications

Abstract

The present invention provides a pharmaceutical composition for preventing and / or treating neuropathic pain or complications, wherein the active ingredients of the pharmaceutical composition include an artemisinin compound and pregabalin, wherein the artemisinin compound is selected from one or more of dihydroartemisinin, artemether and artesunate, preferably dihydroartemisinin. The combined use of dihydroartemisinin and pregabalin of the present invention has obvious advantages in treating the core symptoms of neuropathic pain, reducing drug side effects and reducing drug tolerance.

Description

Technical Field

[0001] The present invention belongs to the field of medicine, and in particular relates to a pharmaceutical composition for preventing and / or treating neuropathic pain or complications. Background Art

[0002] Neuropathic pain refers to pain caused by damage or disease of the somatic sensory nervous system. It is a chronic and intractable pain disease with a prevalence rate of 8% to 10% and an increasing trend year by year. There are about 90 million patients in China who are in urgent need of safe and effective treatment. Epidemiological studies have shown that neuropathic pain is closely related to an increased risk of death from myocardial infarction, stroke, heart failure, and cardiovascular disease. Effective intervention in neuropathic pain is particularly important in the context of an aging society around the world.

[0003] Pregabalin (PGB) is a commonly used clinical first-line drug for the treatment of neuropathic pain. However, epidemiological studies have shown that the overall utilization rate of clinical first-line drugs is only 15.7%. This is closely related to the limited efficacy and tolerance of the drug, toxic and side effects, and truncation reactions. Studies have shown that in about 38% of patients, high doses (600 mg / kg) of pregabalin can temporarily inhibit the transmission of nociceptive signals; and as the duration of medication increases, pregabalin gradually becomes tolerant, and the increase in dose is accompanied by an increased risk of angioedema and hypersensitivity reactions, and patients have to stop using the drug. At present, the drug specifications of pregabalin on the market include 25mg, 50mg, 75mg, 100mg, 150mg, 200mg, and 300mg.

[0004] Patent document CN102648915B discloses a pharmaceutical composition for treating or preventing neuropathic pain, the pharmaceutical composition contains pregabalin and pentoxifylline, and may further contain diclofenac or a pharmaceutically acceptable salt thereof, and the pharmaceutical composition has a better therapeutic effect on neuropathic pain caused by diabetes. However, pregabalin, pentoxifylline and diclofenac or a pharmaceutically acceptable salt thereof have significant side effects and are not suitable for long-term use.

[0005] Patent document CN107149601B discloses that artemisinin and its derivatives have significant intervention effects on neuropathic pain. However, in the process of treating neuropathic pain, artemisinin and its derivatives still have a major defect of slow onset of action, which seriously affects their promotion and use in clinical practice. Summary of the invention

[0006] The object of the present invention is to provide a pharmaceutical composition for preventing and / or treating neuropathic pain or complications.

[0007] The specific technical solution is:

[0008] The present invention provides a pharmaceutical composition for preventing and / or treating neuropathic pain or complications. The active ingredients in the pharmaceutical composition include artemisinin compounds and pregabalin.

[0009] Furthermore, the artemisinin compound in the pharmaceutical composition is selected from one or more of dihydroartemisinin, artemether and artesunate, preferably dihydroartemisinin.

[0010] Furthermore, in the pharmaceutical composition, the weight ratio of the artemisinin compound to pregabalin is 1:(2.5-8.5); for example, the weight ratio of the artemisinin compound to pregabalin is 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3.0, 1:3.1, 1:3.2, 1:3.3, 1:3.4, 1:3.5, 1:3.6, 1:3.7, 1:3.8, 1:3.9, 1:4.0, 1:4.1, 1:4.2, 1:4.3, 1:4.4, 1:4.5, 1:4.6, 1:4.7, 1:4.8, 1:4.9, 1:4.1 :5.0, 1:5.1, 1:5.2, 1:5.3, 1:5.4, 1:5.5, 1:5.6, 1:5.7, 1:5.8, 1:5.9, 1:6.0, 1:6.1, 1:6.2, 1:6.3, 1:6.4, 1:6.5, 1:6.6, 1:6.7, 1:6.8, 1:6.9, 1:7.0, 1:7.1, 1:7.2, 1:7.3, 1:7.4, 1:7.5, 1:7.6, 1:7.7, 1:7.8, 1:7.9, 1:8.0, 1:8.1, 1:8.2, 1:8.3, 1:8.4, 1:8.5.

[0011] Furthermore, the pharmaceutical composition also includes pharmaceutically acceptable excipients.

[0012] Furthermore, the pharmaceutical composition is an oral preparation, an injection, a suppository or a coating.

[0013] Furthermore, the pharmaceutical composition is a liposome preparation, a nanoparticle preparation, a solid dispersant, a self-emulsifier, a transdermal administration agent, a β-cyclodextrin inclusion compound or a phospholipid complex.

[0014] Furthermore, the oral preparation may contain, in addition to the active ingredients of the present invention, pharmaceutically acceptable excipients such as fillers, disintegrants, flavoring agents and wetting agents.

[0015] Furthermore, the filler includes cellulose, mannitol, lactose, cyclodextrin or sorbitol; the disintegrant includes starch, polyvinyl pyrrolidone, sodium starch glycolate, sodium carboxymethyl cellulose or cross-linked polyvinylpyrrolidone; the lubricant includes magnesium stearate, micropowdered silica gel, talc or sodium stearyl fumarate; the flavoring agent includes sucralose, sucrose, neotame or aspartame.

[0016] Furthermore, the injection may contain, in addition to the active ingredient of the present invention, pharmaceutically acceptable excipients, such as sterile water for injection, oil for injection, emulsifier, stabilizer and isotonicity regulator.

[0017] Furthermore, the injection oil includes soybean oil, sesame oil, corn oil, peanut oil, tea oil, cottonseed oil, olive oil, coconut oil, castor oil or safflower oil; the emulsifier includes soybean lecithin, egg yolk lecithin or poloxamer; the stabilizer includes sodium cholate, oleic acid, cholesterol or stearic acid glyceryl ester; the isotonicity regulator includes glycerol, xylitol or glucose.

[0018] Furthermore, the suppository may contain, in addition to the active ingredients of the present invention, pharmaceutically acceptable excipients such as a solubilizing agent, a preservative and a chelating agent.

[0019] Furthermore, the coating agent may contain pharmaceutically acceptable excipients, such as moisturizers, thickeners, chelating agents and cosolvents, in addition to the active ingredients of the present invention.

[0020] Furthermore, the administration routes of the pharmaceutical composition include intravenous, transdermal, intradermal, subcutaneous, intramuscular, intraperitoneal, oral, rectal, intranasal or a combination thereof.

[0021] The present invention also provides the use of artemisinin compounds and pregabalin in combination in the preparation of a drug for preventing and / or treating neuropathic pain or complications.

[0022] Furthermore, the combination comprises the sequential or simultaneous use of artemisinin compounds and pregabalin.

[0023] Furthermore, the complications include one or more of depression, anxiety or cognitive impairment.

[0024] Furthermore, the neuropathic pain includes pain caused by damage or disease of the somatic sensory nervous system, which is a type of chronic pain, and its clinical manifestations include but are not limited to spontaneous pain, hyperalgesia, abnormal pain or paresthesia.

[0025] Further, the weight ratio of the artemisinin compound to pregabalin is 1:(2.5-8.5); for example, the weight ratio of the artemisinin compound to pregabalin is 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3.0, 1:3.1, 1:3.2, 1:3.3, 1:3.4, 1:3.5, 1:3.6, 1:3.7, 1:3.8, 1:3.9, 1:4.0, 1:4.1, 1:4.2, 1:4.3, 1:4.4, 1:4.5, 1:4.6, 1:4.7, 1:4.8, 1:4.9, 1:5. 0, 1:5.1, 1:5.2, 1:5.3, 1:5.4, 1:5.5, 1:5.6, 1:5.7, 1:5.8, 1:5.9, 1:6.0, 1:6.1, 1:6.2, 1:6.3, 1:6.4, 1:6.5, 1:6.6, 1:6.7, 1:6.8, 1:6.9, 1:7.0, 1:7.1, 1:7.2, 1:7.3, 1:7.4, 1:7.5, 1:7.6, 1:7.7, 1:7.8, 1:7.9, 1:8.0, 1:8.1, 1:8.2, 1:8.3, 1:8.4, 1:8.5.

[0026] Furthermore, the drug dosage of the artemisinin compound is 105 mg / d, and the drug dosage of pregabalin is 600 mg / d.

[0027] Furthermore, the drug has the effect of reducing anxiety and disorder side effects, and the reduction refers to the effect relative to the use of pregabalin alone.

[0028] Furthermore, the drug has the effect of shortening the onset time of dihydroartemisinin, and the shortening refers to the time relative to the use of dihydroartemisinin alone.

[0029] Compared with existing drugs for neuropathic pain and / or its complications, the present application has the following effects: it has a definite and significant therapeutic effect on neuropathic pain and its core symptoms; it significantly reduces the drug dosage of pregabalin and significantly reduces the drug tolerance of pregabalin; it significantly reduces the anxiety, disorder and other side effects caused by the long-term use of pregabalin; it significantly shortens the onset time of dihydroartemisinin, and addresses its defect of poor efficacy in the acute phase of neuropathic pain; it is low-cost and simple to prepare. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 Shown are the analgesic efficacy of the drugs alone and in combination.

[0031] Figure 2 A shows the antidepressant efficacy of the drugs alone and in combination (tail suspension test).

[0032] Figure 2 B shows the antidepressant efficacy of the drugs alone and in combination (forced swimming test).

[0033] Figure 3 Shown are the antianxiety effects (open field test) of the drugs alone and in combination.

[0034] Figure 4 A shows the intervention effect of single and combined drugs on cognitive impairment (quadrant II - residence time).

[0035] Figure 4 B shows the intervention effect of single and combined drugs on cognitive impairment (quadrant II - latency to step onto the stage).

[0036] Figure 4 C shows the intervention effect of single and combined drugs on cognitive impairment (quadrant IV - residence time).

[0037] Figure 4 D shows the intervention effect of single and combined drugs on cognitive impairment (quadrant 4 - latency to step onto the stage). DETAILED DESCRIPTION

[0038] The following is a further description of the concept of the present invention and the technical effects produced in conjunction with specific embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of them. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention. The methods are conventional methods unless otherwise specified. The materials can be obtained from public commercial channels unless otherwise specified.

[0039] Example 1 Pre-experimental preparation, model construction and drug administration method

[0040] 1. Experimental Animals

[0041] SPF-grade 8-week-old adult male ICR mice weighing 24–26 g were provided by Beijing Weitonglihua Experimental Animal Technology Co., Ltd. with animal certificate number SYXK-2022-0017.

[0042] 2. Experimental Grouping

[0043] After 4 days of acclimatization, the mice were weighed and subjected to open field test, forced swimming test and tail suspension test. The mice with a body weight of less than 23 g, a center field stay time of less than 15 seconds in the open field test, a forced swimming immobility time of more than 160 seconds, or an immobility time of more than 50 to 100 seconds in the tail suspension test were eliminated. The mice were then randomly divided into sham operation group, model group, dihydroartemisinin group, pregabalin group, double-dose pregabalin group, dihydroartemisinin-pregabalin combination group, and double-dose dihydroartemisinin-pregabalin combination group. Ten mice were selected from each group for analysis in each parallel experiment.

[0044] 3. Methods for establishing a mouse neuropathic pain model

[0045] The present application adopts the spinal nerve ligation (SNL) method to prepare a mouse neuropathic pain model.

[0046] The specific method is as follows: the mice in the model group and each drug treatment group were anesthetized with a small animal ventilator (isoflurane), the transverse process of the sixth lumbar vertebra was exposed under a dissecting microscope, the transverse process was cut off, the 6th, 5th, and 4th spinal nerves were separated, and the 5th spinal nerve was ligated with a No. 6 ophthalmic line, and sutured after surgery. After anesthesia, the sham operation group only exposed the transverse process of the sixth lumbar vertebra, the transverse process was cut off, the 6th, 5th, and 4th spinal nerves were separated, and sutured directly after surgery.

[0047] 4. Method of administration

[0048] The day of modeling / sham operation was designated as D0. From D1 to D17, drugs were administered by gavage once in the morning and at 8 pm, respectively. Among them, mice in each drug treatment group were given the configured drugs, and mice in the sham operation group and the model group were given an equal amount of solvent. The actual gavage volume of each mouse was calculated according to the actual body weight (g) / 30 (g)*0.3ml on the day of gavage. The specific drug concentrations are as follows: dihydroartemisinin is 0.8 mg / ml; pregabalin (single dose) is 4.55 mg / ml (according to clinical practice, the human dose of 300 mg / time, twice a day, is converted to the mouse dose and set as a single dose); pregabalin double dose is 9.1 mg / ml; dihydroartemisinin-pregabalin combination group is 0.8 mg dihydroartemisinin-4.55 mg pregabalin / ml; dihydroartemisinin-pregabalin double dose combination group is 0.8 mg dihydroartemisinin-9.1 mg pregabalin / ml.

[0049] Example 2 Mechanical pain threshold detection and its results

[0050] The mechanical pain threshold of mice in each group at D0, D1, D4, D7, D10, D14, and D17 was tested by the Von Frey method. The higher the pressure of the sensitive probe, the higher the pain threshold. Figure 1 shown.

[0051] D1-17, compared with the sham operation group, the mechanical pain threshold of the model group was significantly reduced ( *** P<0.001), indicating that the mice in the model group had significant and stable symptoms of hyperalgesia.

[0052] D14-17, compared with the model group, the mechanical pain threshold of the dihydroartemisinin group was significantly increased ( & P<0.05), indicating that dihydroartemisinin has a good analgesic effect; however, from D1 to D10, there was no significant difference in the mechanical pain threshold between the dihydroartemisinin group and the model group, indicating that dihydroartemisinin has a longer analgesic effect. In SNL mice, it takes at least 14 days to have a significant analgesic effect. D7, compared with the model group, the mechanical pain threshold of the pregabalin group was significantly increased ( # P<0.05), indicating that pregabalin has a good analgesic effect and takes effect earlier than dihydroartemisinin; however, from D10 to 17, there was no significant difference in the mechanical pain threshold between the pregabalin group and the model group, indicating that the analgesic effect of pregabalin did not accumulate with the extension of medication time, but tolerance occurred. From D1 to D17, the mechanical pain thresholds of the double-dose pregabalin group and the double-dose combination of dihydroartemisinin-pregabalin group were not significantly different from those of the model group at each time point, indicating that better analgesic efficacy or resistance to drug tolerance cannot be achieved by increasing the dosage of pregabalin. From D7 to 17, compared with the model group, the mechanical pain threshold of the dihydroartemisinin-pregabalin combination group was significantly increased ( ％ P<0.05), indicating that the combination of dihydroartemisinin and pregabalin has a good analgesic effect; it is worth noting that the analgesic onset time of the dihydroartemisinin-pregabalin combination group was advanced to the 7th day after administration, which was 3 days earlier than that of dihydroartemisinin alone; and the analgesic effect of the dihydroartemisinin-pregabalin combination group was maintained at least until the 17th day after administration, which was 7 days longer than that of pregabalin alone; further, correlation analysis showed that the mechanical pain threshold of the dihydroartemisinin-pregabalin combination group was positively correlated with the medication time (R 2 =0.2970), indicating that the analgesic effect of the drug combination is cumulative with the prolonged medication time, suggesting that it is more in line with the needs of clinical long-term medication.

[0053] In summary, the combination of dihydroartemisinin and pregabalin can significantly improve the analgesic effect of single medication.

[0054] Example 3 Tail suspension test and its results

[0055] On D18 after surgery, the depressive behavior of mice was detected by tail suspension test. The tail tip of each group of mice was fixed with tape 2 cm away and hung in the test box. The total hanging time was 6 minutes, and the total time the mice stopped struggling within 4 minutes was recorded. The longer the time, the more severe the depression. The results are shown in Figure 2. Figure 2 As shown in A.

[0056] Compared with the sham operation group, the time to stop struggling in the model group was significantly increased ( ** P<0.005), indicating that mice in the model group had depressive-like behaviors.

[0057] Compared with the model group, the time to stop struggling was significantly reduced in the dihydroartemisinin group and the dihydroartemisinin-pregabalin combination group ( ** P<0.005, * P<0.05), indicating that both dihydroartemisinin alone and in combination with pregabalin can achieve significant antidepressant effects. At the same time, there was no significant difference in the time to stop struggling between the pregabalin, double-dose pregabalin, and double-dose dihydroartemisinin-pregabalin groups and the model group, indicating that pregabalin itself has no significant intervention effect on the depressive symptoms of neuropathic pain, and double pregabalin dosage caused irreparable damage to the depression of mice.

[0058] In summary, the combination of dihydroartemisinin and pregabalin increases the antidepressant effect compared with pregabalin alone.

[0059] Example 4 Forced swimming test and its results

[0060] On D18 after surgery, the depressive behavior of mice was detected by forced swimming test. Swimming training was carried out on the day before the experiment. Each group of mice was placed in a deep water area with a depth of more than 16 cm and a temperature of 20°C to swim for 12 minutes. On the day of the experiment, each group of mice was placed in a confined space with a depth of more than 16 cm and a temperature of 20°C. A 6-minute forced swimming test was conducted, and the total time the mice stopped struggling within the last 4 minutes was recorded. The longer the time, the more severe the depression. The results are as follows: Figure 2 As shown in B.

[0061] Compared with the sham operation group, the time to stop struggling in the model group was significantly increased ( * P<0.05), indicating that mice in the model group had depressive-like behaviors.

[0062] Compared with the model group, the time to stop struggling was significantly reduced in the dihydroartemisinin group and the dihydroartemisinin-pregabalin combination group ( *** P < 0.001, * P<0.05), indicating that both dihydroartemisinin alone and in combination with pregabalin can achieve significant antidepressant effects. At the same time, there was no significant difference in the time to stop struggling between the pregabalin, double-dose pregabalin, and double-dose dihydroartemisinin-pregabalin groups and the model group, indicating that pregabalin itself has no significant intervention effect on the depressive symptoms of neuropathic pain, and double pregabalin dosage caused irreparable damage to the depression of mice.

[0063] Compared with the pregabalin group, the time to stop struggling was significantly reduced in the dihydroartemisinin-pregabalin combination group ( ** P<0.005), indicating that the combined use of dihydroartemisinin significantly brought about a good antidepressant effect.

[0064] In summary, the combination of dihydroartemisinin and pregabalin increases the antidepressant effect compared with pregabalin alone.

[0065] Example 5 Open field detection and its results

[0066] Anxiety-relief behavior was tested using an open field test. A square pure black open field test box with a bottom side length of 50 cm and a height of 30 cm was prepared. A square center area with a side length of 30 cm and a distance of 20 cm from the box wall was marked on the bottom. Each group of mice was placed in the open field test box with their heads facing the box wall. The total time the mice stayed in the center area within 4 minutes was recorded. The longer the time, the lighter the anxiety level. The results are shown in the figure. Figure 3 shown.

[0067] Compared with the sham operation group, the central field residence time in the model group was significantly reduced ( *** P<0.001), indicating that mice in the model group had anxiety-like behaviors.

[0068] Compared with the model group, the central field residence time in the dihydroartemisinin group and the dihydroartemisinin-pregabalin combination group was significantly increased ( *** P < 0.001, * P<0.05), indicating that both dihydroartemisinin alone and in combination with pregabalin can achieve significant anxiolytic effects. At the same time, there was no significant difference in the central field residence time between the pregabalin group and the model group, and the central field time in the double-dose pregabalin group was significantly increased compared with the model group. This suggests that the commonly used analgesic dose of pregabalin itself has no significant intervention effect on the anxiety symptoms of neuropathic pain, while high doses have a certain anxiolytic effect.

[0069] In summary, the combination of dihydroartemisinin and pregabalin increases the antianxiety effect compared with pregabalin alone.

[0070] Example 6 Morris water maze test and its results

[0071] Morris water maze test was used to detect cognitive behavior. Prepare the standard Morris water maze for mice and related behavior recording hardware and software. From D1 to D3, the platform was placed in the second quadrant, and each mouse was trained to find the platform for 90 seconds. The software recorded its movement trajectory and performed data analysis; D4, the platform was removed, and each mouse was subjected to a 60-second behavioral test, and the software recorded its movement trajectory and performed data analysis; D5, the platform was placed in the fourth quadrant, and each mouse was trained to find the platform for 90 seconds. The software recorded its movement trajectory and performed data analysis; D6, the platform was removed, and each mouse was subjected to a 60-second behavioral test, and the software recorded its movement trajectory and performed data analysis.

[0072] The Morris water maze is divided into two parts: the second quadrant and the fourth quadrant. Each quadrant is divided into two parts: the training phase (before the platform is withdrawn: the movement time of the mouse in each quadrant is counted) and the test phase (after the platform is withdrawn: the latency time of the mouse before reaching the platform position for the first time is counted). Among them, the data before the platform is withdrawn reflects whether the mouse has passed the cognitive training, and the data after the platform is withdrawn further reflects whether the mouse has cognitive impairment. The results are as follows Figure 4 shown.

[0073] The experimental data before the withdrawal of the second quadrant showed that ( Figure 4 A), the movement time of the sham operation group in the second quadrant was significantly longer than that in the other three quadrants ( *** P<0.001), indicating that they have a good cognitive level; the exercise time of the model group in the second quadrant was not significantly different from that of the other quadrants, indicating that they did not pass the cognitive training and had cognitive impairment; the exercise time of the dihydroartemisinin group, pregabalin group and dihydroartemisinin-pregabalin combination group in the second quadrant was significantly higher than that of the other three quadrants ( *** P < 0.001, ** P<0.005), indicating that they all passed the cognitive training.

[0074] Data after withdrawal shows ( Figure 4 B), compared with the sham operation group, the latency of the model group was significantly increased ( *** P<0.001), indicating cognitive impairment; compared with the model group, the latency to step on the platform was significantly reduced in the dihydroartemisinin group and the dihydroartemisinin-pregabalin combination group ( *** P<0.001), while there was no significant difference in the latency to step onto the platform between the dihydroartemisinin group and the dihydroartemisinin-pregabalin combination group, indicating that dihydroartemisinin alone and in combination with pregabalin significantly improved the cognitive impairment of mice; compared with the dihydroartemisinin group and the dihydroartemisinin-pregabalin combination group, the latency to step onto the platform in the pregabalin group was significantly increased ( **P<0.005), and there was no significant difference in the latency of the pregabalin group compared with the model group, indicating that pregabalin had no effect on repairing cognitive impairment.

[0075] In summary, the combination of dihydroartemisinin and pregabalin increases the effect of repairing cognitive impairment compared with pregabalin alone.

[0076] The experimental data before the withdrawal of the fourth quadrant showed that ( Figure 4 C), the movement time of the sham operation group in the fourth quadrant was significantly longer than that in the first and third quadrants ( ** P<0.005, * P<0.05), indicating that they have a good cognitive level; the exercise time in the fourth quadrant of the model group was not significantly different from that in other quadrants, indicating that they did not pass the cognitive training and had cognitive impairment; the exercise time in the fourth quadrant of the dihydroartemisinin group was significantly higher than that in other quadrants ( ** P<0.005, * P<0.05), indicating that they all passed the cognitive training; the exercise time in the fourth quadrant of the dihydroartemisinin-pregabalin combination group was significantly higher than that in the third quadrant, indicating that their cognitive ability has recovered to a certain extent; the exercise time in the fourth quadrant of the pregabalin group was significantly lower than that in the second quadrant, indicating that they did not pass the new cognitive training after changing channels and had cognitive impairment.

[0077] Data after withdrawal shows ( Figure 4 D), compared with the sham operation group, the latency of the model group was significantly increased ( *** P<0.001), indicating cognitive impairment; compared with the model group, the latency to step on the platform was significantly reduced in the dihydroartemisinin group, pregabalin group, and dihydroartemisinin-pregabalin combination group ( *** P<0.001), indicating that the drugs significantly improved cognitive impairment. Compared with the dihydroartemisinin group and the dihydroartemisinin-pregabalin combination group, the pregabalin group had a significantly increased latency to step onto the platform ( ** P<0.005, * P<0.05), indicating that the intervention effect of pregabalin on cognitive impairment was inferior to that of dihydroartemisinin and the combination of dihydroartemisinin-pregabalin.

[0078] In summary, the combination of dihydroartemisinin and pregabalin increases the effect of repairing cognitive impairment compared with pregabalin alone.

[0079] Although the present invention has been described in detail above by means of general description, specific implementation methods and experiments, the present invention is not limited to the above embodiments, and some modifications or improvements can be made on the basis of the present invention, which is obvious to those skilled in the art. Therefore, these modifications or improvements made on the basis of not departing from the spirit of the present invention all belong to the scope of protection claimed by the present invention.

Claims

1. A pharmaceutical composition for treating neuropathic pain, characterized in that: The active ingredients in the pharmaceutical composition include dihydroartemisinin and pregabalin; the weight ratio of dihydroartemisinin to pregabalin is 1:5.7; The pharmaceutical composition reduces the drug tolerance of pregabalin and shortens the onset time of dihydroartemisinin.

2. The pharmaceutical composition according to claim 1, characterized in that The pharmaceutical composition also includes pharmaceutically acceptable excipients, and the pharmaceutical composition is an oral preparation, an injection, a suppository or a coating.

3. The pharmaceutical composition according to claim 1, characterized in that The drug dosage of dihydroartemisinin is 105 mg / d, and the drug dosage of pregabalin is 600 mg / d.

4. Application of artemisinin compounds and pregabalin in combination for the preparation of drugs for the treatment of neuropathic pain; The artemisinin compound is dihydroartemisinin; The weight ratio of the artemisinin compound to pregabalin is 1:5.7; The drug reduces the drug tolerance of pregabalin and shortens the onset time of dihydroartemisinin.

5. The use according to claim 4, characterized in that: The combination comprises the sequential or simultaneous use of artemisinin compounds and pregabalin.

6. The use according to claim 4, characterized in that: The neuropathic pain includes pain caused by damage or disease of the somatic sensory nervous system.

7. The use according to claim 4, characterized in that: The drug has the effect of shortening the onset time of dihydroartemisinin, and the shortening refers to the effect relative to the use of dihydroartemisinin alone.

8. The use according to claim 4, characterized in that: The drug dosage of the artemisinin compound is 105 mg / d, and the drug dosage of pregabalin is 600 mg / d.

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